Novel model of constrictive pericarditis associated with autoimmune heart disease in interferon-gamma-knockout mice.
Circulation
; 110(18): 2910-7, 2004 Nov 02.
Article
em En
| MEDLINE
| ID: mdl-15505106
ABSTRACT
BACKGROUND:
Constrictive pericarditis represents a serious hemodynamic syndrome that may lead to heart failure. Studies of its pathophysiological mechanisms have been impeded by the lack of an animal model. METHODS ANDRESULTS:
Cardiac myosin-induced experimental autoimmune myocarditis in interferon (IFN)-gamma-knockout (KO) mice results in increased cardiac inflammation and development of severe grossly detectable pericarditis. Using in vivo pressure-volume studies, we found that the acute phase of experimental autoimmune myocarditis in IFN-gamma-KO mice was characterized by reduced left ventricular (LV) volumes compared with wild-type mice. The KO mice exhibited a classic restrictive/constrictive phenotype with decreased cardiac output, increased chamber stiffness, preserved ejection fraction, and impaired diastolic filling, characterized by reduced deceleration time and pressure tracings showing the square root sign similar to that observed in clinical cases of constrictive pericarditis. This phenotype was not associated with the severity of myocarditis but correlated with the presence of grossly detectable adhesive pericarditis present only in the KO group and characterized by increased pericardial inflammation and fibrosis. Comparison of IFN-gamma-KO and wild-type mice matched for the severity of myocardial disease further confirmed that pericarditis, and not myocarditis, was responsible for smaller LV volumes, reduced cardiac output, increased cardiac stiffness, and increased peak filling rate adjusted for end-diastolic volumes in KO mice.CONCLUSIONS:
Autoimmune heart disease in IFN-gamma-KO mice results in increased pericardial inflammation and fibrosis, leading to constrictive phenotype during the acute phase of disease. It represents a novel animal model of constrictive pericarditis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pericardite Constritiva
/
Doenças Autoimunes
/
Interferon gama
/
Modelos Animais de Doenças
/
Miocardite
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Circulation
Ano de publicação:
2004
Tipo de documento:
Article